Capecitabine, Vorinostat, and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer

OBJECTIVES: Primary * Determine the maximum tolerated dose of vorinostat when given in combination with capecitabine and high-dose hypofractionated radiotherapy in patients with nonmetastatic pancreatic cancer. Secondary * Determine the safety and side effect profile of this regimen in these patients. * Determine the response rate in patients treated with this regimen. Correlative * Compare pre- and post-treatment whole-cell HDAC-activity levels in peripheral blood mononuclear cell samples. * Assess chromatin structure and DNA damage in surgical tumor tissue samples. * Assess proliferation and apoptosis by in vivo imaging. OUTLINE: This is a dose-escalation study of vorinostat. Patients receive oral capecitabine twice daily and undergo high-dose hypofractionated radiotherapy once daily on days 1-5 and 8-12. Patients also receive oral vorinostat once daily on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients are evaluated for surgery within 6 weeks after completion of chemoradiotherapy. Patients with resectable disease proceed to surgery. Patients with unresectable disease may receive oral vorinostat once daily and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for correlative laboratory studies. Patients also undergo diffusion-weighted MRI for analysis of in vivo tumor cellularity. After completion of study therapy, patients are followed up periodically for 5 years.